miR‐30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy

Summary Aim Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42...

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Published in:Cardiovascular therapeutics 2015-06, Vol.33 (3), p.89-97
Main Authors: Raut, Satish K., Kumar, Akhilesh, Singh, Gurinder B., Nahar, Uma, Sharma, Vibhuti, Mittal, Anupam, Sharma, Rajni, Khullar, Madhu
Format: Article
Language:English
Subjects:
Animals
Atrial Natriuretic Factor - metabolism
Cardiac hypertrophy
Cardiac Myosins - metabolism
Cardiomegaly - pathology
Cdc42
cdc42 GTP-Binding Protein - biosynthesis
Cell Line
Diabetes Mellitus, Experimental
Diabetic Cardiomyopathies - pathology
Diabetic cardiomyopathy
MicroRNAs - metabolism
miR‐30c
Myocytes, Cardiac - metabolism
Myosin Heavy Chains - metabolism
p21-Activated Kinases - biosynthesis
Pak1
Rats
Rats, Wistar
Streptozocin
Up-Regulation
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Summary:Summary Aim Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42, Pak1, and miR‐30c in the pathogenesis of cardiac hypertrophy in DCM. Methods DCM was induced in Wistar rats by low‐dose streptozotocin‐high‐fat diet for 12 weeks. Cardiac expression of Cdc42, Pak1 and miR‐30c, and hypertrophy markers (ANP and β‐MHC) was studied in DCM vs control rats and in high‐glucose (HG)‐treated H9c2 cardiomyocytes. Results Diabetic rats showed cardiomyocyte hypertrophy, increased heart‐to‐body weight ratio, and an increased expression of ANP and β‐MHC. Cardiac expression of Cdc42 and Pak1 genes was increased in diabetic hearts and in HG‐treated cardiomyocytes. miR‐30c was identified to target Cdc42 and Pak1 genes, and cardiac miR‐30c expression was found to be decreased in DCM rats, patients with DCM, and in HG‐treated cardiomyocytes. miR‐30c overexpression decreased Cdc42 and Pak1 genes and attenuated HG‐induced cardiomyocyte hypertrophy, whereas miR‐30c inhibition increased Cdc42 and Pak1 gene expression and myocyte hypertrophy in HG‐treated cardiomyocytes. Conclusion Downregulation of miR‐30c mediates prohypertrophic effects of hyperglycemia in DCM by upregulation of Cdc42 and Pak1 genes.
ISSN:1755-5914
1755-5922
DOI:10.1111/1755-5922.12113